七氟醚后处理对大鼠肠缺血再灌注损伤的影响

目的 评价七氟醚后处理对大鼠肠缺血再灌注损伤的影响.方法 成年雄性SD大鼠36只,体重200 ～ 220 g,采用随机数字表法,将其分为4组(n=9)∶假手术组(Sham组)、肠缺血再灌注组(I/R组)、缺血后处理组(Ipo组)和七氟醚后处理组(Sevo组).I/R组、Ipo组Sevo组采用结扎肠系膜上动脉60 min,再灌注120min的方法制备肠缺血再灌注模型.Ipo组于再灌注即刻恢复血流30 s后再阻断30 s,重复3次行后处理.Sevo组于再灌注即刻吸入1.15％七氟醚30 min行后处理.再灌注120 min时,处死大鼠,取小肠组织,采用Chui评分法行病理学损伤评分;采用TUNEL法计算凋亡细胞密度;采用比色法检测MDA含量和SOD活性;采用Western blot法检测caspase-3蛋白表达.结果 与Sham组相比,I/R组、Sevo组和Ipo组病理学损伤评分、凋亡细胞密度和MDA含量均升高,SOD活性降低,caspase-3蛋白表达上调(P＜0.05);与I/R组相比,Sevo组和Ipo组病理学损伤评分、凋亡细胞密度和MDA含量均降低,SOD活性升高,caspase-3蛋白表达下调(P＜0.05);Sevo组和Ipo组病理学损伤评分、凋亡细胞密度、MDA含量、SOD活性和caspase-3蛋白表达比较差异无统计学意义(P＞0.05).结论 七氟醚后处理可通过减轻脂质过氧化反应和减少细胞凋亡,减轻大鼠肠缺血再灌注损伤,其保护效应与缺血后处理相似.     

肠缺血再灌注对大鼠脑的影响

目的 评价肠缺血再灌注对大鼠脑的影响.方法 健康雄性成年SD大鼠64只,采用随机数字表法,将其随机分为2组(n=32):假手术组(S组)和肠缺血再灌注组(II/R组),采用Morris水迷宫实验测定认知功能,随后II/R组采用夹闭肠系膜上动脉90min后再灌注的方法制备肠缺血再灌注模型,S组仅分离肠系膜上动脉,不夹闭.于再灌注2、6、12、24 h时各组随机取8只大鼠,经心脏取血2ml后,取肠及脑组织,光镜下观察病理学结果,采用改良Chiu评分法评价肠粘膜损伤程度,采用ELISA法测定血浆TNF-α和IL-6浓度,采用TUNEL法检测皮层脑组织细胞凋亡情况;于再灌注24 h时采用Morris水迷宫实验测试认知功能.结果 S组大鼠肠及脑组织镜下结构未见异常,II/R组再灌注6 h后可见明显肠道和脑损伤.与S组比较,II/R组再灌注2、6、12和24 h时Chiu评分、血浆TNF-α及IL-6浓度升高,再灌注6、12和24 h时细胞凋亡数增加,再灌注24 h时大鼠潜伏期、游泳距离增加,穿越平台次数减少(P＜0.05或0.01),游泳速度差异无统计学意义(P＞0.05).结论 肠缺血再灌注损伤可诱发大鼠脑损伤,引起认知功能减退,可能与炎性介质的释放及神经细胞凋亡有关.

Abstract：

Objective To investigate the effects of intestinal ischemia-reperfusion (I/R) on the brain in rats. Methods Sixty-four healthy male SD rats weighing 250-300 g were randomly allocated to one of 2 groups (n = 32 each): sham operation group (S) and intestinal I/R group (I/R). Intestinal I/R was produced by occlusion of superior mesenteric artery (SMA) for 90 min followed by reperfusion. Eight animals were sacrificed at each of the following time points: 2, 6, 12 and 24 h of reperfusion (T1-4) in each group. After a median sternotomyblood samples were taken from left ventricle for measurement of plasma TNF-α and IL-6 (by ELISA). Intestine and brain tissue was harvested for microscopic examination and detection of apoptosis ( by TUNEL). The cognitive function was tested using Morris water maze at 24 h. Results No abnormality was found in intestine and brain tissue in group S. Intestinal damage and neurodegeneration were detected in group I/R. Intestinal I/R significantly increased cerebral apoptosis in group I/R compared with group S. Plasma TNF-a and IL-6 concentrations were significantly higher at T1-4 in group I/R than in group S. The escape latency and swimming distance were significantly increased, while the number of crossing the platform was decreased in group I/R compared with group S. There was no significant difference in the swimming speed between the 2 groups. Conclusion Intestinal I/R can induce brain injury and lead to cognitive dysfunction. I/R-induced release of inflammatory mediators and neuronal apoptosis are involved in the underlying mechanism.     

小剂量氯胺酮预处理对大鼠肠缺血再灌注损伤的影响

目的 探讨小剂量氯胺酮预处理对大鼠肠缺血再灌注损伤的影响.方法 清洁级健康雄性SD大鼠48只,体重230～270 g,随机分为6组(n=8):假手术组(S组)、氯胺酮+假手术组(KS组)、肠缺血再灌注组(I/R组)、氯胺酮预处理组(K组)、锌原卟啉Ⅸ+氯胺酮预处理组(KZ组)和锌原卟啉Ⅸ组(Z组).采用夹闭肠系膜上动脉根部1 h后再灌注的方法 制备肠缺血再灌注模型.于麻醉前30 min时,S组腹腔注射生理盐水2 ml,K组和KS组均腹腔注射氯胺酮10 mg/kg,KZ组依次腹腔注射氯胺酮10 ms/kg和锌原卟啉Ⅸ5 mg/kg,Z组腹腔注射锌原卟啉Ⅸ5 mg/kg.S组、KS组仅分离肠系膜上动脉,不结扎.于再灌注6 h时处死大鼠,取肠组织测定丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性、血红素加氧酶-1(HO-1)及诱导型一氧化氮合酶(iNOS)的表达,光镜下观察肠组织病理学结果 并采用Chiu评分评价损伤程度.结果 与S组比较,I/R组、KZ组和Z组肠组织MDA含量升高,SOD活性降低,K组MDA含量升高(P<0.05或0.01),SOD活性差异无统计学意义(P>0.05),I/R组、K组、KZ组和Z组肠组织HO-1和iNOS表达上调(P<0.05或0.01),肠组织病理学损伤加重;与I/R组比较,K组肠组织MDA含量降低,SOD活性升高,肠组织HO-1表达上调,iNOS表达下调(P<0.05),肠组织病理学损伤减轻,KZ组和Z组以上指标差异无统计学意义(P>0.05).结论 小剂量氯胺酮预处理可减轻大鼠肠缺血再灌注损伤,可能与氯胺酮上调肠组织HO-1表达,下调iNOS表达有关.     

异丙酚对大鼠肠缺血再灌注时肠粘膜细胞凋亡的影响

目的评价异丙酚对大鼠肠缺血再灌注（I／R）时肠粘膜细胞凋亡的影响。方法24只SD大鼠随机分为3组（n=8），假手术组（S组）仅分离肠系膜上动脉（SMA）；肠缺血再灌注组（I／R组）阻断SMA1h；异丙酚组（P组）阻断SMA前30min腹腔注射异丙酚100mg／kg。于再灌注3h处死大鼠，取回肠末端组织，电镜及TUNEL法观察肠粘膜上皮细胞凋亡情况，并计算肠粘膜上皮细胞凋亡指数；测定肠粘膜超氧化物歧化酶（SOD）活性、丙二醛（MDA）及神经酰胺（CER）含量，RT-PCR法测定肠粘膜鞘磷脂酶（SMase）mRNA表达。结果与S组比较，I／R组肠粘膜SOD活性降低，MDA含量、CER含量、肠粘膜上皮细胞凋亡指数及SMasemRNA表达升高（P〈0．05或0．01）；与I／R组比较，P组MDA含量、CER含量、肠粘膜上皮细胞凋亡指数及SMasemRNA表达降低，S01）活性升高（P〈0．05或O．01）。I／R组肠粘膜SOD活性与CER含量呈负相关（r＝-0．775，P〈0．01），肠粘膜上皮细胞凋亡指数与CER含量呈正相关（r=0．852，P〈0．01）；P组肠粘膜上皮细胞凋亡指数与CER含量呈正相关（r=0．782，P〈0．01）。结论异丙酚可抑制大鼠肠缺血再灌注时肠粘膜上皮细胞凋亡，可能与清除氧自由基、下调SMasemRNA表达、减少CER生成有关。     

异丙酚对大鼠肠缺血再灌注后肺损伤的影响

目的探讨异丙酚对大鼠肠缺血再灌注后肺损伤的影响。方法32只成年SD大鼠,随机分为4组（n=8）,缺血再灌注组（I/R组）缺血1 h,再灌注2 h;异丙酚1组（P1组）在缺血前10 min、异丙酚2组（P2组）在再灌注前10min静脉注射异丙酚10mg,kg,然后以10mg·kg^-1·h^-1持续输注,余处理同I/R组;假手术组（C组）不行缺血再灌注及异丙酚输注。所有大鼠在再灌注120 min时处死。光镜下观察肺组织形态学及细胞凋亡;测定肺组织超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量及含水量。结果I/R组光镜下可见大量肺泡塌陷、实变,肺实质水肿及中性粒细胞浸润聚集。与C组比较,I/R组及P2组肺组织细胞凋亡计数增加,I/R组肺组织SOD活性降低,MDA含量升高,含水量升高（P＜0．05或0．01）;与I/R组比较,P1组SOD活性升高,MDA含量降低（P＜0．01）。结论细胞凋亡参与了大鼠肠缺血再灌注后肺损伤的发生,肠缺血前给予异丙酚可明显减轻肠缺血再灌注后肺损伤。     

色甘酸钠对大鼠肠缺血再灌注损伤的作用

目的 探讨肥大细胞膜稳定剂色甘酸钠对大鼠肠缺血再灌注损伤的作用。方法 32只SD大鼠随机分为4组（n=8）：假手术组（S组）、缺血再灌注组（I/R组）、缺血再灌注＋色甘酸钠25 mg/kg组（C1组）及缺血再灌注＋色甘酸钠50 mg/kg组（C2组）。采用肠缺血45 min再灌注1h制备肠缺血再灌注损伤模型,C1组、C2组再灌注前15min腹腔注射色甘酸钠。再灌注1h后,取小肠组织,光镜下观察小肠粘膜病理学改变,进行Chiu评分,电镜下观察小肠粘膜的超微结构,测定小肠肿瘤坏死因子-α（TNF-α）及组胺含量,进行肠粘膜肥大细胞（IMMC）计数,并测定类胰蛋白酶表达。结果 肠缺血再灌注导致小肠Chiu评分、TNF-α含量、IMMC计数及类胰蛋白酶表达增加,组胺含量降低,IMMC出现胞浆颗粒明显减少,颗粒包膜相互融合形成细胞内空泡等脱颗粒现象;色甘酸钠25、50mg/kg可减弱肠缺血再灌注导致的上述改变,且50mg/kg的作用更明显。Chiu评分与TNF-α、组胺、类胰蛋白酶水平有相关性,相关系数分别为0．532、-0．770（P＜0．05）。结论 色甘酸钠25、50mg/kg可抑制IMMC活性,减少TNF-α的释放,从而减轻了大鼠肠缺血再灌注损伤;色甘酸钠50mg/kg的效果较好。     

缺血预处理-后处理对大鼠肠缺血再灌注损伤的影响

目的 评价缺血预处理.后处理对大鼠肠缺血再灌注损伤的影响.方法 清洁级成年雄性SD大鼠40只.体重225～275 g,随机分为5组(n=8):假手术组(S组)仅分离肠系膜上动脉(SMA),不夹闭;肠缺血再灌注组(IIR组)采用夹闭SMA 60 min,再灌注60 min的方法制备肠缺血再灌注损伤模型;缺血预处理组(IPr组)夹闭SMA 10 min,再灌注10 min,余同IIR组;缺血后处理组(IPo 组)夹闭SMA 60 min后,再灌注30 s,缺血30 s,反复3次,再灌注60 min;缺血预处理.后处理组(IPr-IPo组)先行缺血预处理,再行缺血后处理,操作过程同IPr组和IPo组.于再灌注60 min时各组取肠粘膜组织,观察肠粘膜形态并行Chiu评分,检测丙二醛(MDA)含量,超氧化物歧化酶(SOD)及髓过氧化物酶(MPO)活性,同时采集动脉血样检测血浆肿瘤坏死因子α(TNF-α)及白细胞介素6(IL-6)浓度.结果 与S组比较,其余各组Chiu评分、MDA含量、MPO活性、血浆TNF-α与IL-6浓度升高,SOD活性降低(P<0.05).与IIR组比较,IPr组、IPo组及IPr-IPo组Chiu评分、MDA含量、MPO活性、血浆TNF-α和IL-6浓度降低.SOD活性升高(P<0.01).与IPr组和IPo组比较,IPr-IPo组Chiu评分和MDA含量降低,SOD活性升高(P<0.05).IPr组与IPo组各指标比较差异无统计学意义(P>0.05).结论 缺血预处理-后处理可减轻大鼠肠缺血再灌注损伤,较单独应用时效果好.     

电刺激迷走神经对肠缺血再灌注大鼠肝损伤的作用

目的 研究电刺激迷走神经对肠缺血再灌注大鼠肝损伤的作用。方法 30只成年雄性Wistar大鼠，行双侧颈部迷走神经切断术后，随机分为3组（n=10），对照组（C组）：仅暴露腹腔；肠缺血再灌注组（Ⅱ／R组）：暴露腹腔后，夹闭肠系膜上动脉（SMA）1h，再灌注2h；迷走神经刺激＋肠缺血再灌注组（VNS组）：在夹闭SMA前及再灌注开始时分别以5V、2ms和1Hz强度的电能持续刺激左颈部迷走神经远端20min；颈动咏插管以监测平均动咏压（MAP）。再灌注2h时处死大鼠，进行肝组织病变程度评价，测定肝组织肿瘤坏死因子-α（TNF-α）、核转录因子-κB（NF-κB）的表达以及血浆TNF-α浓度。结果与C组比较，Ⅱ／R组再灌注期MAP下降，血浆TNF-α及肝组织TNF-α、NF-κB水平升高，肝组织病变程度加重（P〈0．05或0．01）；电刺激迷走神经可减弱上述改变。结论电刺激迷走神经可减轻肠缺血再灌注后肝损伤。     

缺血预处理-后处理对大鼠肠缺血再灌注损伤的影响

Objective To evaluate the effects of ischemic preconditioning-postconditioning on the intestinal ischemia-reperfusion (IR) injury in rats. Methods Forty healthy male SD weighing 225-275 g were randomly assigned into 5 groups ( n = 8 each): group I sham operation (group S) ; group II intestinal IR (group IIR); group Ⅲ ischemic preconditioning (group Ipr); group IV ischemic postconditioning (group Ipo); group V Ipr+ Ipo. The rats were anesthetized with intraperitonel 20% urethane 5 ml/kg. Superior mesenteric artery (SMA) was occluded for 60 min followed by 60 min reperfusion. In group S, SMA was isolated but not occluded. In group Ipr, SMA was occluded for 10 min followed by 10 min reperfusion, and the rest procedures were performed using the method described in group IIR. In group Ipo, 60 min ischemia was followed by three 30 s episodes of ischemia at 30 s intervals for reperfusion. In group Ipr+ Ipo, Ipr was performed followed by Ipo and the procedures were performed using the methods described in group Ipr and Ipo. The animals were killed at 60 min of reperfusion. The intestinal tissues were immediately removed for determination of MDA content, SOD and MPO activities and the degree of damage to intestinal mucous membrane was scored according to Chiu score. Arterial blood samples were taken for determination of plasma concentrations of TNF-α and 1L-6. Results Compared with group S, Chiu score, MDA content, MPO activity, and plasma concentrations of TNF-α and IL-6 were significantly increased, whereas SOD activity decreased in the other 4 groups ( P < 0.05). Chiu score, MDA content, MPO activity, and plasma concentrations of TNF-α and IL-6 were significantly decreased, whereas SOD activity increased in group Ipr, Ipo and Ipr + Ipo as compared with group IIR ( P < 0.05). Chiu score and MDA content were significantly lower, whereas SOD activity higher in group Ipr + Ipo than in group Ipr and Ipo ( P < 0.05). No significant differences were detected in the indices between group Ipr and group Ipo ( P > 0.05). Conclusion Ischemic preconditioning-postconditioning can attenuate the intestinal IR injury in rats, and the efficacy is better than that of either Ipr or Ipo alone.     

缺血预处理-后处理对大鼠肠缺血再灌注损伤的影响

Objective To evaluate the effects of ischemic preconditioning-postconditioning on the intestinal ischemia-reperfusion (IR) injury in rats. Methods Forty healthy male SD weighing 225-275 g were randomly assigned into 5 groups ( n = 8 each): group I sham operation (group S) ; group II intestinal IR (group IIR); group Ⅲ ischemic preconditioning (group Ipr); group IV ischemic postconditioning (group Ipo); group V Ipr+ Ipo. The rats were anesthetized with intraperitonel 20% urethane 5 ml/kg. Superior mesenteric artery (SMA) was occluded for 60 min followed by 60 min reperfusion. In group S, SMA was isolated but not occluded. In group Ipr, SMA was occluded for 10 min followed by 10 min reperfusion, and the rest procedures were performed using the method described in group IIR. In group Ipo, 60 min ischemia was followed by three 30 s episodes of ischemia at 30 s intervals for reperfusion. In group Ipr+ Ipo, Ipr was performed followed by Ipo and the procedures were performed using the methods described in group Ipr and Ipo. The animals were killed at 60 min of reperfusion. The intestinal tissues were immediately removed for determination of MDA content, SOD and MPO activities and the degree of damage to intestinal mucous membrane was scored according to Chiu score. Arterial blood samples were taken for determination of plasma concentrations of TNF-α and 1L-6. Results Compared with group S, Chiu score, MDA content, MPO activity, and plasma concentrations of TNF-α and IL-6 were significantly increased, whereas SOD activity decreased in the other 4 groups ( P < 0.05). Chiu score, MDA content, MPO activity, and plasma concentrations of TNF-α and IL-6 were significantly decreased, whereas SOD activity increased in group Ipr, Ipo and Ipr + Ipo as compared with group IIR ( P < 0.05). Chiu score and MDA content were significantly lower, whereas SOD activity higher in group Ipr + Ipo than in group Ipr and Ipo ( P < 0.05). No significant differences were detected in the indices between group Ipr and group Ipo ( P > 0.05). Conclusion Ischemic preconditioning-postconditioning can attenuate the intestinal IR injury in rats, and the efficacy is better than that of either Ipr or Ipo alone.     

亚甲蓝对兔肠缺血再灌注时肺损伤的影响

目的评价亚甲蓝（MB）对兔肠缺血再灌注时肺损伤的影响。方法健康新西兰白兔36只,体重2.5～3.5 kg,雄雌不拘,随机分为3组（n=12）,假手术组（S组）不夹闭肠系膜上动脉;缺血再灌注组（I/R组）：夹闭肠系膜上动脉1 h,再灌注3 h;MB组再灌注前即刻静脉注射亚甲蓝10 mg/kg。再灌注3 h时,抽取静脉血,测定血清肿瘤坏死因子-α（TNF-α）、白细胞介素-8（IL-8）及总蛋白浓度;取右肺下叶组织,测定肺组织湿/干重比（W/D）和Na^＋-K^＋-ATPase活性;测定支气管肺泡灌洗液（BALF）中蛋白浓度,并计算其与血清总蛋白浓度的比值,表示肺通透指数;光镜及电镜下观察肺组织结构,并进行中性粒细胞（PMN）计数。结果与S组比较,I/R组血清TNF-α、IL-8浓度及BALF蛋白浓度、PMN计数、肺通透指数和W/D升高,Na^＋-K^＋-ATPase活性降低,MB组PMN计数、BALF蛋白浓度和肺通透指数升高,Na^＋-K^＋-ATPase活性降低（P〈0.05或0.01）;与I/R组比较,MB组血清TNF-α、IL-8及BALF蛋白浓度、PMN计数、肺通透指数和W/D降低,Na^＋-K^＋-ATPase活性升高（P〈0.05或0.01）。MB组肺组织结构损伤轻于I/R组。结论再灌注前即刻静脉注射亚甲蓝10 mg/kg可减轻兔肠缺血再灌注时肺损伤,与抑制肺组织Na^＋-K^＋-ATPase活性降低及减轻炎性反应有关。     

Protective effects of pretreatment with Radix Paeoniae Rubra on acute lung injury induced by intestinal ischemia/reperfusion in rats

Objective： To investigate the effect of pretreatment with Radix Paeoniae Rubra （RPR） on acute lung injury induced by intestinal ischemia/reperfusion in rats and its protective mechanism.
Methods： Thirty-two Wistar rats were randomly divided into four groups： Sham-operation group, ischemla/ reperfusion group （I/R group ）, RPR-pretreatment group and hemin group. The model of intestinal ischemia/ reperfusion was established by clamping the superior mesenteric artery for 1 hour followed by 2-hour reperfusion. The effect of RPR on the expression of heme oxygenase-1 （HO-1） in lung tissues was detected by immunohistochemistry and morphometry computer image analysis. Arterial blood gas analysis, lung permeability index, malondialdehyde （MDA） and superoxide dismutase （SOD） contents in lungs were measured. The histological changes of lung tissue were observed under light microscope.
Resalts： The expression of HO-1 in RPR-pretreatment group and hemin group was obviously higher than that in sham-operation group and I/R group （ P 〈 0.01 ）. The level of MDA and lung permeability index in RPR-pretreatment and hemin group were significantly lower than those in I/R group （P〈0.01 or P〈0.05）, while the activity of SOD in RPR-pretreatment and hemin group was obviously higher than that in I/R group （P〈0.01）. Under light microscope, the pathologic changes induced by I/R were significantly attenuated by RPR.
Conclusion： Intestinal ischemia/reperfusion may result in acute lung injury and pretreatment with RPR injection can attenuate the injury. The protective effect of RPR on the acute lung injury is related to its property of inducing HO-1 expression and inhibiting lipid peroxidation.     

再灌注期间给予富氢液对大鼠全脑缺血再灌注损伤的影响

目的 评价再灌注期间给予富氢液对大鼠全脑缺血再灌注损伤的影响.方法 成年雄性SD大鼠72只,月龄2.0～2.5个月,体重260～300 g,采用随机数字表法,将其随机分为3组(n＝24):假手术组(S组)、脑缺血再灌注组(I/R组)和富氢液组(H组).I/R组和H组采用四血管阻塞法(缺血15 min)制备全脑缺血再灌注损伤模型.H组于再灌注6h时腹腔注射0.6 mmol/L富氢液5ml/kg,I/R组给予等容量生理盐水.再灌注24h时,每组处死18只大鼠,取海马组织,测定丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)含量、NF-κB活性、活化的caspase-3表达;再灌注72 h时,处死6只大鼠,取脑组织,HE染色,光镜下观察海马CA1区病理学结果,进行海马CA1区正常锥体细胞计数.结果 与S组比较,I/R组海马组织MDA、TNF-α、IL-6含量和NF-κB活性升高,活化caspase-3表达上调,正常锥体细胞计数减少(P<0.05);与I/R组比较,H组海马组织MDA、TNF-α、IL-6含量和NF-κB活性降低,活化caspase-3表达下调,正常锥体细胞计数增多(P<0.05).H组脑组织海马CA1区病理学损伤程度轻于I/R组.结论 再灌注期间给予富氢液可减轻大鼠全脑缺血再灌注损伤,其机制与抑制脂质过氧化反应、炎性反应和细胞凋亡有关.     

缺血后处理对大鼠局灶性脑缺血再灌注损伤的影响

目的探讨缺血后处理对大鼠局灶性脑缺血再灌注损伤的影响。方法36只雄性SD 大鼠随机分为3组(n=12),对照组:即单纯缺血再灌注组;缺血后处理15s组(I-15 s组):大脑中动脉线栓阻闭(MCAO)90 min后,再灌注15 s,缺血15 s,反复3次;缺血后处理30 s组(I-30 s组):MCAO 90 min后,再灌注30 s,缺血30 s,反复3次。再灌注24 h后对所有动物行神经功能障碍评分(NDS),然后取大脑测定脑梗死容积。结果再灌注24 h后I-15 s和I-30 s组NDS与对照组比较差异无统计学意义(P>0.05)。再灌注24 h后脑梗死容积I-15s组为(271±97)mm3,I-30 s组为(217±85)mm3,小于对照组[(378±103)mm3](P<0.01),I-15 s和I-30 s组比较差异无统计学意义(P>0.05)。结论缺血后处理可减轻局灶性脑缺血再灌注大鼠脑的病理性损伤。     

肠缺血再灌注对大鼠脑组织小胶质细胞活化的影响

目的 探讨肠缺血再灌注对大鼠脑组织小胶质细胞活化的影响.方法 清洁级健康成年雄性SD大鼠128只,体重250-300 g,采用随机数字表法,将其随机分为2组(n=64):假手术组(S组)和肠缺血再灌注组(I/R组).I/R组采用夹闭肠系膜上动脉90 min后再灌注的方法制备肠缺血再灌注损伤模型.于再灌注2、6、24、48 h时观察肠粘膜病理学结果,并行Chiu评分;取脑组织,计数活化的小胶质细胞,计算小胶质细胞活化率,测定脑组织活性氧(ROS)、MDA含量及SOD活性、NO含量、一氧化氮合酶(NOS)及诱导型一氧化氮合酶(iNOS)活性.结果 与S组比较,I/R组肠组织Chiu评分、脑组织活化的小胶质细胞数、小胶质细胞活化率、ROS、NOS和iNOS活性、MDA和NO含量升高,SOD活性降低(P＜0.05或0.01);I/R组再灌注6-48 h脑组织ROS、NOS和iNOS活性、MDA和NO含量依次升高,脑组织SOD活性及肠组织Chiu评分依次降低,脑组织活化的小胶质细胞和小胶质细胞活化率于再灌注24h时达峰值(P＜0.05或0.01).结论 肠缺血再灌注可通过激活脑组织小胶质细胞,激活NOS和促进ROS生成,从而诱发脂质过氧化反应,该作用作为肠缺血再灌注诱发大鼠脑损伤的机制.     

帕瑞昔布钠对大鼠局灶性脑缺血再灌注损伤的影响

目的 评价帕瑞昔布钠对大鼠局灶性脑缺血再灌注损伤的影响.方法 雄性SD大鼠54只,体重300～350 g,随机分为3组(n=18):假手术组(S组)、缺血再灌注组(I/R组)和帕瑞昔布钠组(P组).I/R组和P组采用电凝左侧大脑中动脉、夹闭双侧颈总动脉60 min时进行再灌注的方法制备脑缺血再灌注模型.P组分别于缺血前15 min和再灌注11 h时静脉注射帕瑞昔布钠4 mg/kg,S组和I/R组给予等容量生理盐水.再灌注72 h时进行神经功能评分,然后取脑组织,测定脑梗死体积、肿瘤坏死因子-α(TNF-α)及脑源性神经营养因子(BDNF)表达水平.结果 与S组比较,I/R组神经功能评分降低,脑梗死体积扩大,TNF-α和BDNF表达上调(P＜0.05);与I/R组比较,P组神经功能评分升高,脑梗死体积缩小,TNF-α表达下调,BDNF表达上调(P＜0.05).结论帕瑞昔布钠可减轻大鼠局灶性脑缺血再灌注损伤,其机制与抑制炎性反应和上调BDNF表达有关.     

含饱和氢气肾保存液对大鼠肾脏冷缺血再灌注损伤的影响

目的 评价含饱和氢气肾保存液对大鼠肾脏冷缺血再灌注损伤的影响.方法 健康雄性Wistar大鼠24只,周龄8～10周,体重200～ 250 g,采用随机数字表法,将其随机分为3组(n=8):对照组(H1组)大鼠仅切除右肾;普通肾保存液组(H2组)大鼠采用冷缺血再灌注模型,用4℃普通HC-A肾保存液对左肾行冷灌注和冷保存;含饱和氢气肾保存液组(H3组)大鼠操作同H2组,灌注液及保存液换用自制的4℃含饱和氢气HC-A肾保存液.于再灌注24 h时抽取下腔静脉血样,测定血清BUN、Cr、TNF-α和IL-6浓度;切取左肾,测定肾组织MDA和8-羟基脱氧鸟苷(8-OHdG)含量,光镜下观察肾组织病理学结果.结果 与H1组相比,H2组和H3组大鼠血清BUN、Cr、TNF-α和IL-6浓度及肾组织MDA和8-OHdG含量均升高(P＜ 0.05);与H2组相比,H3组血清BUN、Cr、TNF-α和IL-6浓度及肾组织MDA和8-OHdG的含量均降低(P＜0.05).H1组肾组织形态结构未见明显异常,H2组肾小管损伤明显,H3组肾小管损伤较H2组减轻.结论 含饱和氢气肾保存液可明显减轻大鼠肾脏冷缺血再灌注损伤.     

15-F2t-isoprostane在大鼠肠缺血再灌注损伤中的作用

目的 评价异构前列腺素15-F2t-isoprostane在大鼠肠缺血再灌注损伤中的作用.方法 健康雄性SD大鼠32只,体重230 ～ 255 g,采用随机数字表法,将其随机分为4组(n=8):假手术组(S组)、肠缺血再灌注组(I/R组)、血栓烷A2(TXA2)受体拮抗剂SQ-29548组(SQ组)和二甲基亚砜组(DMSO组).采用阻断肠系膜上动脉60 min,再灌注120 min的方法制备肠缺血再灌注损伤模型.SQ组及DMSO组分别于夹闭肠系膜上动脉前30 min腹部皮下注射SQ-29548或二甲基亚砜2μmol/kg.于再灌注120 min时取肠段,观察肠粘膜形态学,并行Chiu评分,取肠粘膜组织,检测髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)活性和丙二醛(MDA)、乳酸(LD)含量;采集动脉血样,检测血清二胺氧化酶( DAO)活性及15-F2t-isoprostane、内皮素-1(ET-1)和血栓烷B2(TXB2)浓度.结果 与S组比较,其余各组Chiu评分、DAO活性、15-F2t-isoprostane及TXB2浓度均升高(P＜0.05),SQ组LD和MDA含量、MPO和SOD活性及ET-1浓度差异无统计学意义(P＞0.05);与I/R组比较,SQ组Chiu评分、LD含量、DAO和MPO活性及ET-1浓度降低,SOD活性升高(P＜0.05).结论 15-F2t-isoprostane可通过激活TXA2受体,增加ET-1生成及促进中性粒细胞在肠粘膜聚集参与大鼠肠缺血再灌注损伤过程.